Submissions for variant NM_001276345.2(TNNT2):c.3G>A (p.Met1Ile)

dbSNP: rs1289914935

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Mayo Clinic Laboratories, Mayo Clinic	RCV001508034	SCV001713934	uncertain significance	not provided	2019-09-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002358636	SCV002619599	uncertain significance	Cardiovascular phenotype	2019-02-25	criteria provided, single submitter	clinical testing	The p.M1? variant (also known as c.3G>A), located in coding exon 1 of the TNNT2 gene, results from a G to A substitution at nucleotide position 3. This alters the methionine residue at the initiation codon. Variations that modify the initiation codon (ATG) are expected to result in loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame; however, loss of function of TNNT2 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV002529034	SCV003279158	uncertain significance	Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3	2023-01-18	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with TNNT2-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 487631). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change affects the initiator methionine of the TNNT2 mRNA. The next in-frame methionine is located at codon 60.
Genome-Nilou Lab	RCV003451294	SCV004182136	uncertain significance	Dilated cardiomyopathy 1D	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003451295	SCV004182147	uncertain significance	Cardiomyopathy, familial restrictive, 3	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003451293	SCV004182158	uncertain significance	Hypertrophic cardiomyopathy 2	2023-11-04	criteria provided, single submitter	clinical testing
Human Genetics Bochum, Ruhr University Bochum	RCV003451294	SCV004704494	uncertain significance	Dilated cardiomyopathy 1D	2023-04-28	criteria provided, single submitter	clinical testing	ACMG criteria used to clasify this variant: PVS1_MOD, PM2_SUP
All of Us Research Program, National Institutes of Health	RCV004001215	SCV004828144	uncertain significance	Cardiomyopathy	2023-05-31	criteria provided, single submitter	clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000656211	SCV000678405	likely pathogenic	Wolff-Parkinson-White pattern	2017-07-14	no assertion criteria provided	research	This variant was identified in an individual with Wolff-Parkinson-White syndrome